In recent years, type 2 diabetes and its chronic complications have become a threat to human health as the “third killer”. According to statistics, standardized prevalence rate of type 2 diabetes in China has rapidly increased from 0.9 percent in the early 1980's to the current 5.21 percent; and the standardized prevalence rate of impaired glucose tolerance is 4.76 percent. Long-term hyperglycemia associated with type 2 diabetes results in the damage of many tissues and organs, which in turn lead to a variety of diabetic chronic complications, such as coronary heart disease, atherosclerosis, cerebrovascular disease and other diabetic macrovascular diseases, diabetic nephropathy, diabetic retinopathy and other diabetic microangiopathy, diabetic neuropathy, diabetic foot, diabetic maculopathy, diabetic cataract, diabetic glaucoma, refractive changes, iris and ciliary body diseases.
At present, most of the oral hypoglycemic agents that are on the market are expensive or have some adverse reactions, which cause poor compliance of patients. The pathogenesis of the diabetic chronic complications is not entirely clear, and there is no ideal drug in the clinical treatment. Therefore research and development of drugs that are low cost, but show high efficiency and low toxicity that not only has hypoglycemic effect but also prevent and treat diabetic chronic complications will have important clinical significance and market value.
Mangiferin, a natural polyphenol is from Liliaceae plants such as Anemarrhena asphodeloides Bunge. etc., molecular weight: 422, structural formula: C19H18O11, and its chemical structure is as follows:

Mangiferin is a natural antioxidant. Pharmacological study shows that mangiferin has a variety of biological activity, such as anti-oxidation, anti-tumor, anti-bacterial, anti-virus, hypoglycemic, hypolipidemic effect, anti-inflammatory, choleretic, immunomodulation, etc. Mangiferin can lower blood glucose and lipid levels of diabetic rats or mice by oral or intraperitoneal injection. The potential mechanism of hypoglycemic is probably by increasing insulin sensitivity [Miura T, Ichiki H, Hashimoto I, et al. Antidiabetic activity of a xanthone compound, mangiferin, Phytomedicine, 2001, 8(2):85-87].
In recent years, more evidence show that the hyperglycemia, oxidative stress and diabetic chronic complications are closely related. Muruganandan's research shows that in the streptozotocin-induced diabetic rats, mangiferin by intraperitoneal injection can control the lipid peroxidation, and can reduce the glycosylated hemoglobin and serum creatine phosphate Kinase (CPK) of the diabetes rats and its complications due to chronic oxidative damage. Mangiferin can also protect animals avoiding the damage of heart and kidney. [Muruganandan S, Gupta S, Kataria M, et al. Mangiferin protects the streptozptocin-induced oxidative damage to cardiac and renal tissues in rats. Toxicology, 2002, 176(3):165-173]. The LD50 of mangiferin by intraperitoneal injection once is 365 mg/kg in rat [Yu shengmin, Zhong ming. The research advance of pharmacology effects of the mangiferin. Chinese Journal of Traditional Medical Science and Technology, 1999, 6(3):199-200]. We can see that mangiferin is safe.
Because mangiferin cannot dissolve in water, there is limitation such as its bioavailability, and formulation.
Berberine (Ber) is an isoquinoline alkaloid that is extracted from the root and bark of Coptis chinesis Franch (Ranunculaceae coptis plant). Berberine is the main ingredient of the coptis. Molecular formula: C20H18NO4, molecular weight: 336.37. Its chemical structure is as follows

Pharmacological research of berberine shows that it has a variety of biological activities, such as anti-bacterial, anti-virus, hypoglycemic, anti-abnormal heart rate, lower blood pressure, anti-tumor, lipid-lowering, etc.
Animal experiments show that berberine can reduce the blood glucose of the normal mice, and the alloxan diabetic and chronic complications mice, and the spontaneous diabetic and chronic complications KK mice. The effect is significantly, the duration is long, while berberine can improve glucose tolerance of the KK mice. In recent years, clinical research has proven that berberine has the effects of anti-diabetes and improves its chronic complications, especially in the treatment of type 2 diabetes and chronic complications. The mechanism of the hypoglycemic effect may be by inhibiting the liver gluconeogenesis and/or promoting the glycolysis of the peripheral organizations, that is the non-insulin-dependent. But only under the conditions of moderately high glucose level (for example, 11.1 mmol/L), will berberine have significant hypoglycemic effect. However, under conditions of seriously high glucose level (for example, 22.2 mmol/L), the hypoglycemic effect of the berberine disappear. Berberine mainly applies to impaired glucose tolerance, abnormal fasting blood glucose and stable blood glucose of the diabetics [Yin jun, Hu renming, Chen mingdao, et al. Comparison of glucose consumption effects of Mmetformin, troglitazone and berberine on the HepG2 cells. Chinese Journal of Endocrinology and Metabolism, 2002, 18(6):488-489].
In recent years, studies have shown that sustained hyperglycemia can increase the activity of aldose reductase in cells which leads to diabetic neuropathy, diabetic retinopathy and a variety of vascular diseases. It is significant to inhibit aldose reductase activity on the treatment of chronic diabetic complications. Many scholars' studies showed that berberine can inhibit the activity of aldose reductase [Liu Changshan; Dong Yanhu; Pang Linan; et al. The effects of baicalin and berberine on proteinuria and glomerular ultrastructure in alloxan-induced diabetic rats. CHINESE JOURNAL OF DIABETES, 1996, 4(3):163].
Regarding the treatment dose, berberine is safe. Its side effects are few. We do not find any adverse reactions when berberine was used for long. we don't find any adverse reactions when berberine was taken 2.0 g once orally [Ji yubin. The effective composition and pharmacological action of Chinese medicine, Harbin: Heilongjiang Science and Technology Press, 2004, 77].
The bioavailability of berberine is very low. In a certain blood glucose range, berberine may play hypoglycemic role. As a result, the use of berberine in diabetic patients is limited significantly.